Download The normal and diseased pericardium: Current concepts of

240
J AM CaLL CARDIOL
1983;1:240--51
The Normal and Diseased Pericardium:
Current Concepts of Pericardial Physiology, Diagnosis and Treatment
DAVID H. SPOmCK, MD, DSc, FACC
Worcesrer , Massac husetts
The past quarter century has seen remarkable contributions to understanding the role of the pericardium in
health and disease and to diagnostic methods in the context of significant changes in the clinical spectrum of
acute pericarditis, pericardial effusion and their sequelae. Anatomic studies have demonstrated pericardial ultrastructure and its relation to function and delineated
the pericardiallymphatics and their participation in inflammation and tamponade. Physiologic investigations
have revealed the pericardium's mechanical, membranous and ligamentous functions and its role in ventrlcular interaction, pericardiaI modification of cardiac responses during acute cardiocirculatory loading and effects
on diastolic function (and, at high filling pressures, systolic function), including reduction by pericardial fluid
of true filling pressure-the myocardial transmural
pressure. The diastolic mean pressure plateau and phasic
venoatrial pressure and flow during cardiac tamponade
have been further characterized and the mechanisms
producing pulsus paradoxus have been elucidated, including the importance of inspiratory increase in right
ventricular filling. A far reaching compensatory response to tamponade has been revealed, particularly adrenergic stimulation, and, over time, blood volume expansion. Right heart tamponade and low pressure
tamponade have been identified and the importance of
the pericardium in the restrictive dynamics of right ven-
The pericardium has fascin ated physicians since antiquity
(I ), largel y becau se pericardial syndromes produce a range
of often spectacular clinical and physiolo gic abnormalities
and becau se the pericardium is susceptible to involvement
by every kind of disease . The last quarter century has seen
five major book s on the pericardium and its disorders (26) and brill iant advances in elucidating pericardial dynamics, particularl y by cardiology groups led by Shabetai and
Fro m the Division of Cardiology . SI. Vincent Hospital and Universi ty
of Massachu sett s Medical School . Worcester , Massachu setts.
Address for reprints: David H . Spodi ck . MD. DSc . Director of Cardiology. SI. Vincent Hospital. 25 Winthrop Street . Worcester. Massachusett s 0 1604.
1;) 1983
by the American College of Cardiology
tricular myocardial infarction has been demonstrated.
Constrictive pericarditis, and the currently more common
effusive-constrictive pericarditis, have been studied, in
depth, clinically and hemodynamically.
Cardiography in pericardial disease now includes Mmode and two-dimensional echographic studies, enabling rapid diagnosis and further physiologic study in
cardiac tamponade and constriction . The four stages of
typical electrocardiographic evolution in acute pericarditis and atypical variants have been codified and characteristic PR segment deviations identified. The nonetiologic role of acute pericarditis in arrhythmias has
been clarified in prospective clinical and postmortem
investigations. Electric alternation has been elucidated
and its relation to cardiac " swinging" has been at least
partly explained. Special roles now exist for contrast
roentgenography , computed tomography (especially for
cysts) and radionuclide imaging. Clinical advances in pericardial disease include changes in the prevalence of established etiologies and identification of new etiologies,
for example, immunopathic processes to explain recurrent pericarditis and the post-injury (including postoperative) pericardial syndrom es. New forms of constriction-uremic, postoperative, radiation-have appeared
in increasing numbers. The pericardial rub has been
characterized and codified, confirming a typical threecomponent structure (with frequent exceptions).
Fowler <7-19). Guntheroth (20 ,2 1). Redd y (22), Friedm an
(23-25) and a host of physiologists (26-38). Clinical and
laboratory investigations have clarified the hemodynamics
and the nonin vasive regi stration of pericardial diseases and
have delineated the function s of the normal pericardium in
facilitating cardiac action and chamber inter action s. Disease
may compromise pericardial function s and con vert the pericardium from the heart ' s protector to its deadl y enem y.
Because of space limitations I have necessarily conden sed this review of salient contributions of the past 25
years into a synthesis of state-of-the-science and state-ofthe-art concepts and have largely excluded discussion of
experimental and clinical method ology. Recent work sup0735-1097/8310 I0240-12$03.00
J AM cou, CARDIOl
NORMAL AND DISEASED PERICARDIUM
1983;1:240-5 I
ports some and refutes other earlier studies; important references more than 25 years old are found in reference 6.
241
Table 1. Physiology of the Normal Pericardium
Mechanical Function: Promotion of Cardiac Efficiency. Especially During Hemodynamic Overloads
I. Relatively inelastic cardiac envelope
Pericardial Anatomy
Ultrastructure
Gross pericardial anatomy, including mesothelial. fibrous,
elastic, vascular and lymphatic elements, is well understood;
even "subgross" analysis, the dynamic orientation of fibers
in the parietal pericardium, has been characterized (6). Ferrans et al. (39) and Roberts and Spray (40) recently reported
ultrastructural details, including serosal cell microvilli, that
presumably bear friction and facilitate fluid and ion exchange. Although oblique during diastole, these become
more perpendicular during systole. Despite a basal lamina,
pericardial mesothelial cells detach easily. Yet, during systole, the visceral pericardial serosa becomes corrugated and
the cells bulge and thicken. Indeed, the mesothelial cell
monolayer has considerable overlap and marked interdigitations between adjacent cells, a design that would permit
changes in the surface configuration but maintain mechanical stability. Among the many cell constituents are actin
filaments, involved in active change in cell shape, and cvtoskeletal filaments, providing structural support.
Significance of Pericardial Lymphatics
Miller et al. (41) extensi vely studied the cardiopericardial
lymphatics. Myocardial lymph drains to the subepicardium
and ultimately to the mediastinum and right heart cavities.
In heart failure, hydropericardium results from interference
by elevated central venous pressure with myocardial venous
and lymph drainage. Inflammations damage the visceral
pericardium, also interfering with epicardial venous and
lymph flow, with loss of interstitial fluid from the myocardium to the pericardial space. Because most pericarditis with
effusion probably is myopericarditis, all inflammatory effusions may exude through the epicardial surface.
Pericardial Physiology:
A Synthesis of Laboratory
and Clinical Observations
Table I presents a concept derived from experimental and
clinical observations (2-38,42)-a synopsis of the complicated roles of the pericardium and its components. These
roles are divided into mechanical. membranous and ligamentous functions (4). Mechanical functions relate to relative stiffness of the parietal pericardium, its effects as a
fluid-filled chamber at slightly subatmospheric pressure and
incompletely understood circulatory "feedback" regulation
by way of pericardial neuroreceptors and mechanoreceptors.
Membranous functions result from the physical presence of
A. Limitation of excessive acute dilation
B. Protection against excessive ventriculoatrial regurgitation
C. Maintenance of normal ventricular compliance (volume-elasticity relation)
D. Defense of the integrity of the Starling curve: Starling mechanism operates uniformly at all intraventricular pressures because presence of pericardium:
I. Maintains ventricular function curves
Limits effect of increased left ventricular end-diastolic
pressure
3. Supports output responses to
a) venous inflow loads and atrioventricular valve regurgitation (especially acute)
b) rate fluctuations
4. Hydrostatic system (pericardium plus pericardial fluid)
distributes hydrostatic forces over epicardial surfaces
a) Favors equality of transmural end-diastolic pressure
throughout ventricle. therefore uniform stretch of muscle fibers (preload)
b) Constantly compensates for changes in gravitational
and inertial forces. distributing them evenly around the
heart
~
E. Ventricular interaction; relative pericardial stiffness
I. Reduces ventricular compliance with increased pressure in
the opposite ventricle (e.g .. limits right ventricular stroke
work during increased impedance to left ventricular
outflow)
2. Provides mutually restrictive chamber favoring balanced
output from right and left ventricles integrated over several cardiac cycles
3. Permits either ventricle to generate greater isovolumic
pressure from any volume
F. Maintenance of functionally optimal cardiac shape
II. Provision of closed chamber with slightly subatmospheric pressure in which:
A. The level of transmural cardiac pressures will be low. relative to even large increases in "filling pressures" referred to
atmospheric pressures
B. Pressure changes aid atrial filling via more negative pericardial pressure during ventricular ejection
III. "Feedback" cardiocirculatory regulation via pericardial servomechanisms
A. Neuroreceptors (via vagus): lower heart rate and blood
pressure
B. Mechanoreceptors: lower blood pressure and contract spleen
IV. ?? Limitation of hypertrophy associated with chronic exercise
Membranous Function: Shielding the Heart
I. Reduction of external friction due to heart movements
II. Barrier to inflammation from contiguous structures
Ill. Buttressing of thinner portions of the myocardium
A. Atria
B. Right ventricle
IV. Defensive immunologic constituents in pericardial fluid
V. Fibrinolytic activity in mesothelial lining
Ligamentous Function: Limitation at' Undue Cardiac Displacement
242
J AM COLL CARDIOL
1983:1:240- 51
the perica rdium. Ligamentous function limits cardiac displacem ent. Mechanical funct ions and the beha vior of intrapericardial pre ssure largel y explain both helpful and harm ful
per icard ial influences dur ing circ ulatory ove rload, and the
dynami cs of tamponade , co nstrictio n and pul sus parad oxus.
Alth ough removal of the pericardium has little effect on
ventricular function. at any ca rdiac volume per icardie ctomy
decr eases diastolic and de veloped pressures. Indeed . ventricles without a peric ard ium have less stee p diastol ic pressure-vo lume curv es. as see n with volume loadin g and increasi ng filling pre ssures . At eleva ted diastolic pressuresespecia lly when unilateral. as in acute volume overlo adthe perica rdium becomes restrict ive: chronic overloading
abolishes the restriction as a result of pericardial enlargement and ventricular hypertrophy (38) . Although the peri card ium primarily affects dia stolic function , it should second aril y affec t systolic performanc e , even though it may do
so only at very high filling pre ssure s (42 ).
Pericardial pressure curves resemble a mirror image of
the pressure in the adja cent card iac chamber. At normal
cavi tary pre ssure s , pericardial transmural pressure is O.
becau se pericardial pre ssure is app roximately equal to , and
varies with , pleural pre ssure at the same hydro static level.
Pericard ial pre ssure affe cts myocardial transmural pressure
by the relation: transmural pre ssure = cavitary pre ssure
minus adjacent intrapericardial pressure . Becau se myoca rdia l transmural pre ssure is the actual chamber distendin g
(that is , filling) pressure . the norm ally negati ve pericardi al
pressure produces a distending pre ssure that is higher than
cavi tary pre ssure; thu s , left ventricular tra nsmural pressure
= left ventricular pre ssure minus (negative) per icardial
pressure = left ventricular pressure plus pericardial pressure .
Normal respiratory effects. Because the pericardium
transmits important respiratory effe cts, inspiratory reduction
of pleural pressure reduces peri cardial, right atrial, right
ventri cular, pulmonary wedge and sys temic arterial pressures by a few millimeters of mercury . Because pericardial
pre ssure decreases more than atri al pressure , right atrial and
other central transmural pressures increase. augmenting right
heart filling . Inspiration thu s increases right ventricular preload , an effec t that varies inversely with pleural pressure
and directly with syste mic venous pre ssure . Although pulmon ary arte ry flow velocity increases with inspir ation . both
transmu ral pre ssure and flow decrease in the aorta and peripheral arteries at a tim e when sys temic venous return is
incre asing. Moreover, augmented inspiratory right ventricular output " poo ls" temporarily in the lungs. and left heart
filling is reduced . Although left ventricular tran smural pressure increas es with inspiratio n, this slightly incre ases left
ventric ular "afterload," contributing to reduced left ventricu lar output. Thus, respiratory changes in arterial blood
pressure vary directly with changes in pleural pressure.
Pressure breathing. Positive end-expiratory pressure
and intermittent positive pre ssure bre athing increase pul-
SP(JDlCK
mon ary artery transmural pressure. res ulting in increase d
rig ht ventric ular size. The per icard ium impos es ventric ular
interactio n and septal bul ging so that left ventricular chamber co mpliance and size decrease. shift ing the left ventricular pressure-volume relation to a stiffer curve (2). Positive
end-ex piratory pressure and intermi ttent positi ve pressure
breathin g thu s tend to decrease ca rdiac o utput and have long
been contraindicated in ca rdiac tamp onade and other low
output states (6) .
Cardiac Tamponade
Mechanisms (Fig. 1). Cardiac tamponade is defined as
hemodynamically significant cardiac compression by accumulating pericardial cont ent s that evokes and defeats
compensatory mechanisms. Experimental and clinical investiga tio ns (2,3,43) have clar ified the mechanisms of tampon ade and compensatory res ponses. The key effect of relentl essly increasing intraperica rdia l pressure is progressive
reduction of ventricular volume , producing rapidly rising
diastol ic pressures that resis t ventricular filling to the point
where eve n a good ejec tio n fractio n ca nnot avert a critically
reduced stroke volume at any heart rate . The ch ange from
negative to positi ve per icardi al pressure , with both ventricles filling against a common (pericardium plus fluid ) stiffness , evo kes corresponding incre ases in left and right atrial
pre ssures. Because tran smural pressure-cavitary pressure
minus (now positive) per icard ial pressure- is thereby reduced , the distending (filling) pressure progressively
decreases.
Alth ough the right ventricle is compressed durin g tamponade (44) . and its outflow tract collapses in early diastole
(45 ,46) , it expands durin g inspir ation . Pericardial pre ssure
qu ickly exceeds early dia stol ic atrial pressure (16), impeding atrial emptying and the corresponding reduction in pre ssure- visible as amputation of the atr ial y descent. Absence
of the y de scent with a prom inent x descent is characteristic
of pure tamponade and impli es that the atria fill only dur ing
ventric ular ejec tion co nsistent with slightly decreased
compression due to sys tolic reduction in cardiac volume .
The course of ventric ular filling is inco mpletely understood ,
but it is delayed and the ventricle s may fill only durin g atrial
sys tole (45)-a likel y eve nt at least at rapid heart rates.
Extreme tamponade causes per icard ial pressure to exceed
cav itary pressure throughout diastole (47) . Th is produces
per sistentl y negati ve myocardi al transmural pressure . sugges ting filling by dia stol ic suction (5) .
Compensatory responses (Fig . 1). In response to increased sys te mic venous pressure . increased blood volume
supports ca rdiac filling (but only with sufficient time-this
increase is not seen in rapid intraperic ardial hemorrhage).
Adrenergic stimulation and increased atrial pressur e evoke
increased systemic and pulmonary venous pressures and
tachycardia. which tend to maint ain cardiac output at low
J AM Call CARDlOl
NORMAL AND DISEASED PERICARDI UM
243
1993: I:24G-51
t -
Tamponade
/
A Stimulates
Compensation::::' T
Y Opposes
tINTRAPERICARDIAL
PRESSURE
J,
+Ventricular Volume
J,
A+Ventricular
tBlood
" 1~
Volume
tUlmonary~tAtrial pressure
J,
tSystemic &
venous pressure
aOh y oar di 4
' \
!
filling~+Stroke volumeo......-
1
~~cardiac
~
~
~ +Ventricular end-
systolic volume
tejectionffraction
t
Output
+
~arterial
pressure
·'··"i···' ...,...
Inotropic effect
".~
\
A D R ENE R G I CST I M U L A T ION
stroke volumes (however, heart rates in clinical tamponade
are often only modestly increased) . Adrenergic stimulation
also increases peripheral resistan ce to support decreasing
arterial pressure, but a most important consequence is its
inotropic effect. which impro ves the ejection fraction as a
result of greater systolic emptying and therefore greater
stroke output.
Effects of tamponade on coronary flow. Coronary artery flow is reduced by tamponade and may become retrograde during systole (48-50) (although retrograde flow
may be normal within intramural arteries). Flow disturbance s are not surprising if one con sider s the diastolic pressure "vise" clamping the myocardium (43.51). It is not
clear when significant myocardial ischemia occurs. except
in severe experimental tamponade . in which there are selective subendocardial hypoperfusion and hemorrhages (50).
In cases of less severe tamponade , the decrease in coronary
flow may be proportional to the reduced work of the heart.
Pulsus Paradoxus
Mechanism (Fig. 2). Pulsu s paradoxus-exaggeration
of the normal inspiratory decrease in systemic blood pressure-has been extensively investigated (13.20-28) . Although normal respiratory pressure changes are greater for
the right side of the heart. in tamponade pulsus paradoxus
involve s fluctuations in aortic flow and pressure similar to
those in the pulmonary artery-evidence for the increased
effe ct on ventricular interaction of a tight (though yielding)
peric ardium. Pulsus paradoxus is always the net effect of
several mechanisms of individually varying contributions in
a given ca se.
In tamponade , pulsus paradoxus implies a very large
reduction in ventricular volume (25). Its mechanism resembles that of normal breathing, except that inspiratory pericardial pressure briefly decreases (but less than pleural pressure) , then increases as the right ventricle fills. Absolute
cardiac filling is less than normal, but directional changes
Figure l , Physiology of cardiac tamponade including compensatory
mechanisms. Decreased ventricular filling through external compression
and reduced transmural pressure (see text) results in reduced stroke vo lume.
cardiac output and arterial pressure and increased atrial and venou s pressures . Compensatory response s (italics) (open-headed arrows directed
upward) support the points of attack of tamponade (ope n reverse
arrowheads>.
in flow and filling related to respiration remain the same.
Thu s. inspiration accelerates flow in the venae cavae to
increa se right heart filling (11,13 ,14.17). Increased right
ventricular volume causes the interventricular septum to
bulge to the left and increa ses pericardial pressure, further
decreasing left ventricular tran smural pressure . (Left ventricular output can decrease within a beat of beginning inspiration [52]. suggesting an additional, poorly understood
contribution to pulsus paradoxus .) External compression by
pericardial pressure and internal compression by septal shift
reduce left ventricular volume so that the left ventricle operates on a steeper Starling curve and resists filling even
more during inspiration. (The mitral valve may open during
inspiration onl y with atrial systole .) Thu s. left ventricular
stroke output decreases , as is reflected in the inspiratory
decrease in arterial flow and pressure. The difference between inspiratory and expiratory measurements is augmented by two other factor s: I) the time for the inspiratory
increase in right ventricular output to cross the lungs and
appear in the left ventricle, which is partly a function of
heart rate, and 2) the transmission of inspiratory negati ve
pleural pressure to the aorta and systemic arteries. (To an
unknown degree the lungs may act as a capacitor. " pooling"
right ventricular output during inspiration and abolishing or
reversing the pulmonary arter y-left atrial gradient to reduce
left atrial filling.) Left ventricular embarrassment is reflected
in systolic time intervals by a greater than normal inspiratory
increase in left ventricular pre-ejection period and decrease
in ejection time index (53).
244
J AM CaLL CARDIOL
SPOOleK
1983;1:240-51
PULSUS PARADOXUS
INSPIRATION
MRTERIAL FLOW
AND PRESSURE
~(----­
tCaval flow
~INTRAPLEURAL
PRESSURE
~
tRA filling
~LV
~
t
tRY filling
~
Transmural Pressure
/'
tPERICARDIAL PRESSURE
tRY volume ~
Left shift
of IV septum
~
)
+
T
~LV
Output+~LVETI
~LV
filling+~preload+tPEP
~LV
t
APPARENT COMPLIANCE
t
/
LV Compression
Figure 2. Pulsus paradoxus. Inspiration decreases intrapleural pressure
with sequential results differing from normal because pericardial pressure
increases and left ventricular (LV) transmural pressure decreases after an
increase in right ventricular (RV) volume further increases pericardial
pressure. Not shown: transient initial decrease in pericardial pressure; decrease in pleural pressure decreasing aortic flow and pressure; capacitor
function of lungs, pooling right ventricular output to decrease left atrial
inflow (see text). IV = interventricular; LVETI = left ventricular ejection
time index; PEP = pre-ejection period; RA = right atrium.
Absence of pulsus paradoxus. Pulsus paradoxus may
be absent in certain situations. Pulsus paradoxus requires
filling of both ventricles against a common pericardial stiffness plus respiratory changes alternately favoring right and
left heart filling. Advanced left ventricular hypertrophy or
severe left heart failure may maintain left ventricular filling
pressures well above right ventricular and pericardial pressures. In these cases, pericardial pressure matches only right
ventricular filling pressure, because both are determined by
the compliance of the tense pericardial sac, while left ventricular filling pressure is determined by greatly reduced
compliance owing to hypertrophy, dilation or fibrosis. In
atrial septal defect, the increased systemic venous return is
balanced by shunting to the left atrium. Severe aortic incompetence produces regurgitant filling great enough to damp
respiratory fluctuations. Also, respiratory changes may not
be measureable in severe tamponade with extreme
hypotension.
Right heart tamponade is seen both with a low compliance left ventricle that does not manifest pulsus paradoxus
and after cardiac surgery. After surgery. loculated pericardial fluid may cause systemic congestion with appropriate
dynamics, but left heart diastolic pressures do not match
and systemic pulsus paradoxus does not occur. Low pressure
tamponade (2,54) occurs in some patients with pericardial
fluid, but symptoms are few and there is no hypotension.
Right-sided pressures are slightly raised with abnormal pulse
contours, because of only slightly increased pericardial pressure equilibrating with right atrial pressure. This occurs as
a stage between lax and "tight" pericardial effusions and
in effusions complicated by low blood volume. Any further
decrease in blood volume can precipitate florid tamponade
at lower pericardial pressure than occurs with normal or
increased blood volume.
Management of cardiac tamponade. Definitive management is removal of pericardial fluid by paracentesis or
surgical drainage. Pericardial catheterization has been introduced to permit optimal drainage, minimal trauma and
protection against refilling (6,55). Recently, subxiphoid extrapleural surgical drainage (56,57) has effectively relieved
tamponade and permitted digital and endoscopic pericardial
exploration. Based on the physiology of tamponade (Fig.
1), medical management is designed either to attack key
points in the tamponade sequence or to bolster the compensation sequence, or both. These methods include: 1)
blood volume expansion with intravenous fluids; 2) stroke
volume increase with inotropic agents, either those like dopamine that do not increase systemic resistance or those like
norepinephrine that support systemic resistance in severe
hypotension; 3) the use of afterload-reducing agents (58)
in patients with adequate blood pressure; and 4) combined
therapy (for example, blood volume expansion plus afterload reduction). Despite the effect of vasodilator drugs and
volume expansion on experimental tamponade, trials in patients who are not hypovolemic have been disappointing:
prompt drainage of effusions is the treatment of choice (59).
Constrictive Pericarditis
Constriction is less common and less experimentally studied
than tamponade but its hemodynamics are well known (25). The heart is compressed when its volume approximates
pericardial volume in diastole. Like tamponade. constriction
thus severely limits ventricular filling with equalization of
left and right heart filling pressures. but unlike tamponade,
the heart is encased in a quasi-unyielding shell that does not
transmit fluctuating pleural pressure. Thus. there is minimal
respiratory change in cardiac pressures, though jugular venous pressure may increase during inspiration (Kussmaul's
sign). Any inspiratory decrease in arterial pressure in pure
constriction is slight-nearly always less than 10 mm Hg:
any more suggests residual tamponading fluid or pulmonary
disease.
In constriction, end-diastolic right ventricular pressure is
J AM cou, CARDIOl
NORMAL AND DISEASED PERICARDIUM
245
1983:1:240-5 1
with pericardit is have suggestive but nondiagnostic pressures . Intravenou s fluid loads provoke the chara cteristic diastolic restriction curves (64) .
Previously report ed anecdotally (65). the intermediate
syndrome , effusive-constrictive pericarditis in patient s with
simultaneous constriction and a layer of tamponading fluid,
has been carefully analyzed (66) . Because it is usually dominated by tamponade dynam ics, fluid remo val reveals clinical and hemod ynam ic constriction immediately or after further pericardial fibrosis.
at least one-third of its systolic pressure (which is usually
30 mm Hg or more). Unlike tamponade , venous and atrial
pressures show prominent y and x troughs. As in the normal
pericardium and in tamponade , the x descent occurs during
ventricular ejection when the atrioventricular valves move
toward the outflow tracts. Diastolic pressure has an early
dip usually followed by a plateau of diastasis that is at a
common pressure load for both ventricles ("square root
sign") (5). Becau se the atrioventricular valves are open,
the atrial y descent is the result of the dip and the accompanying torrential early diastolic ventricular filling that terminates abruptly in association with a loud third heart sound
as the ventricles reach their constricted limit (5). (Evidenc e
of ventricle-chest wall conta ct in produc ing a third heart
sound [60] has been challenged [61]). A few patients with
some " give" in the constricting tissue have a telediastolic
" atrial kick " in ventricular pressure and a corresponding
fourth heart sound (62). Myocardial inotropic function is
preserved (63) unless there is intrinsic myocardial disease ,
including atrophy in chronic constriction or coronary involvement by scar tissue , or both . Balloon flotation catheters
perm it early physiologic diagnosis (Fig . 3). Constrictive
physiology resemble s that of restrictive cardiomyopathy except that in myopath y, diastolic filling is usually less rapid
and the left ventricle usually remains less compliant than
the right ; as a result , left ventricular diastolic pressure is
usually higher.
Latent (occult) constriction. Some patients with nonspecific symptoms and often a history of disease consistent
Cardiography of Pericardial Disease
El ectrocardiogram
Evolutionary ST-T changes. The traditional quasi -specific evo lutionary ST-T change s of acute pericard itis (6)
have been codified in four stages (any of which may not be
recorded) (67,68); stage I, ST segment deviations; STage /I .
return of ST jun ctions to baseline and flattening of the T
wave; stage Ill , T wave inversions; and stage IV, restituti on
to prepericarditis tracing. Variability of response was recognized including typical and atypical variants of this process . Typical stage I ST elevations in most leads that evo lve
to any other stage remain highly specific . The principal
differential diagnosis of the stage 1 " typical" electrocardiogram of acute pericarditis is the apparently normal variant
••early repolarization "; frequent among neurot ic and psy-
Figure 3. Bedside diagnosis of cons/ric/ion. Unretouched
pressure tracings from patient's chart showing (to p) . prominent
x and y descents in pulmonary capillary wedge (PCW) tracing
(pressure = 22-23 mm Hg). Bottom, pullthrough from right
ventricle (RV) to right atrium (RA) ; high right ventricular
diastolic pressure rebounding from " dip" to more than onethird of right ventricular systolic pressure; right atrial pressure
with prominent x and y descents. C iO . = cardiac output.
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246
J AM COLL CARDIOL
1983:I:240-51
chotic persons. The amplitude ratio, ST junction/T wave of
0.25 or less in lead V6, was 100% specific for "early repolarization" (69). Although widespread PR segment deviations occur much more often with acute pericarditis and
the ST vector is more likely to be to the left of the QRS
vector, these are imperfect discriminators (70).
PR segment deviations. A "new" finding, previously
overlooked because of the optical illusion of ST deviation
when the natural TP baseline is ignored, is PR segment
deviation-depression in most leads; elevation in aVR-a
highly sensitive sign of unknown specificity (67,68). Among
50 patients with uncomplicated acute pericarditis and classic
stage I ST segment deviations, 41 had PR segment deviations. The ST (1) vector was oriented left-anterior-inferior,
consistent with the generalized subepicardial ventricular
myocarditis of acute pericarditis; the PR vector was oriented
right-posterior-superior-directly opposite to the P vectorrepresenting the corresponding atrial myocarditis. Wide dispersion of the T vector in stage III was consistent with
inhomogeneity of post-injury ventricular recovery. Ten nondiagnostic or less diagnostic electrocardiographic patterns
were described, including three normal and "nonspecific"
tracings, four variants of the typical sequence and three
atypical variants simulating local myocardial injury (71,72).
A subsequent investigation of the earliest electrocardiographic changes (that is, when diagnosis may be urgent)
revealed that 43% had atypical or nonspecific tracings (73).
Some patients with only PR segment deviations shortly developed typical stage I ST changes. Thus, a diagnostic electrocardiographic pattern developed soon after onset in about
two-thirds of patients (72).
Electrical alternans. Although not the only etiology of
serious pericardial effusions, metastatic malignancy is the
principal cause of increasing identification of electrical alternans, mostly alternating QRS or QRS-T, though P-QRST ("total") alternation remains pathognomonic for tamponade (74). During pericardiocentesis, prompt disappearance of alternation with the first relatively small fluid decrement usually accompanies disproportionately great relief
of symptoms and lessening signs of cardiac compression
(74). This reverses the usual sequence that provoked circulatory embarassment-the last small increment precipitates acute tamponade (the "last straw" phenomenon). Although this suggested a hemodynamic factor in alternans,
echocardiography shows that the common correlate is
"swinging" of the heart with one excursion over each two
cycles (75). Large cardiac pendular and rotary arcs have
been shown experimentally (76), but to cause alternation
the periodicity must synchronize with half the heart rate.
Yet, more than one mechanism may be involved because
not every swinging heart shows alternation, and irregular
("syncopated") 2: I alternans with atrial ectopic beats has
now been reported (77). Moreover, electrical alternation
during tamponade by only 200 ml of fluid (total pericardial
SI'ODICK
contents) in a patient with a very thick parietal pericardium
suggests a causative role for pericardial stiffness (65).
Echocardiography
Pericardial effusion. Echocardiography has proved highly
reliable for diagnosing pericardial effusion (Table 2) (75).
Prospective studies of M-mode echocardiography delineated
small, moderate and large effusions (78), although fine
quantitation of effusion size has not been successful. But
the sequence of accumulation provides a gross estimate:
Fluid first appears as increased separation of epicardium and
posterior pericardium during systole, progressing to separation during systole and diastole. Next, with moderatesized effusions there is continuous separation of the epicardial and pericardial echoes, with the pericardial echo flat
Table 2. Echocardiograrn in Pericardial Effusion and Cardiac
Tamponade (NB: varying sensitivities and specificities)
I. Pericardial effusion
A. Echo-free space-posterior to LV (small to moderate effusion)
-posterior and anterior (moderate to large
effusion)
-behind left atrium (large to very large
effusion)
B. Decreased movement of posterior pericardium-lung interface
C. RV pulsations brisk (with anterior fluid)
D. Aortic root movement abnormal or attenuated
E. "Swinging heart" (large effusions)
Periodicity I: I or 2: I
RV and LV walls move synchronously
Mitral/tricuspid pseudoprolapse
Alternating mitral E-F slope and aortic opening excursion
II. Cardiac tamponade: changes of effusion plus
A. RV compression
RV diameters decreased
Early diastolic collapse of outflow tract
B. Inspiratory effects (with pulsus paradoxus)
RVexpands
IV septum shifts to left
LV compressed
Mitral D-E amplitude decreased
-E-F slope decreased or rounded
-open time' decreased
Aortic valve' opening decreased; premature closure
Echographic stroke volume decreased
C. Notch in RV epicardium during isovolumic contraction
D. Coarse oscillations of LV posterior wall
Ill. 2-D echocardiography: most of the above plus
A. RA free wall indentation during late diastole or isovolumic
contraction.
B. LA free wall indentation (cases with fluid behind LA)
C. SVC and IVC congestion (unless volume depletion)
'Often difficult to define during pericardial effusion: mitral valve may open only
with atrial systole during inspiration. IV = interventricular: IVC = inferior vena
cava; LA = left atrium; LV = left ventricle; RA = right atrium; RV = right
ventricle: SVC = superior vena cava: 2D = two-dimensional.
NORMAL AND DISEASED PERICARDIUM
J AM cou, CARDIOl
247
1983:1:240-51
or moving slightly. In the absence of adhesions, fluid also
appears anteriorly in moderate to large effusions. The pericardial clasp of the left atrium (6) prevents most posterior
fluid from penetrating behind it, but very large effusions
often extend behind the mitral anulus and lower left atrium
and into the pericardium's oblique sinus. Diagnostic problems arise from left pleural effusions, epicardial fat, tumor
tissue, adhesions and enlargement of other cardiovascular
structures. Exaggerated cardiac motion, particularly
"swinging," often is associated with pseudoprolapse and
false systolic anterior movement of the atrioventricular valves
with large effusions.
Tamponade and pulsus parodoxus. Tamponade shows
all these findings and also progressive compression of the
right ventricle (44) with early diastolic collapse of its outflow
tract (45). Pulsus paradoxus is associated with inspiratory
leftward movement of the interventricular septum as the
right ventricle expands at the expense of the left. often with
premature mid-systolic closure of the aortic valve and delayed opening of the mitral valve (which may only be opened
by atrial systole) during inspiration.
Two-dimensional echocardiography. This has improved diagnosis both because more structures are seen (and
in a more dynamic way) and because findings responsible
for false positive and negative M-mode diagnoses of effusion, including pericardial adhesions, are identified. Clotting of intrapericardial blood and subsequent organization
to the point of adhesions and fibrosis has been observed as
a progressive increase in the intensity of pericardial space
echoes (79). Serial echocardiography has proved valuable
in following the course of pericardial effusions and in detecting hemodynamic compromise.
Adhesive pericardial disease and constriction. In these
conditions, the echocardiogram has been helpful but relatively nonspecific (80,81). Pericardial thickening is suggested by a condensed or doubled echo that may move with
the left posterior wall echo, with or without an intervening
(presumably fluid-filled) space. Constriction may reduce
cavity size, but most consistently imposes flattening of posterior wall motion in mid- to late diastole, usually with no
posterior "depression" after atrial systole; the post-P wave
endocardial echo often moves less than I mm posteriorly.
The atria are dilated. (These signs are not pathognomonic
and can be seen with restrictive cardiomyopathy and acute
cardiac dilation producing restriction by a normal pericardium.) The mitral E-F slope may be rapid, with early mitral
closure. Though atrial systole makes little or no impression
on the posterior wall, after the P wave it often produces
brisk posterior and subsequent anterior motion of the interventricular septum; that is. the sudden increase in left ventricular volume displaces the septum because the posterior
wall cannot "give." (This is not seen in restrictive cardiomyopathy and is distinguished from right ventricular volume overload in which anterior septal motion begins later.
with ventricular systole.) During inspiration both interatrial
and interventricular septa bulge to the left. At very high
right ventricular diastolic pressure, the pulmonary valve
opens prematurely, showing brisk diastolic posterior motion, implying right ventricular pressure transiently exceeding pulmonary artery pressure. After atrial systole there may
be marked inspiratory deepening of the pulmonary valve A
wave (82). In two-dimensional echocardiograms, the pericardium appears as an immobile single or double encasement of the ventricles that abruptly ends ventricular expansion; atrioventricular valves are hyperactive.
Roentgenography and Imaging
Because no size or shape of the cardiopericardial silhouette
is specific for pericardial lesions, plain chest X-ray films
are of little diagnostic value, except to identify calcifications
at its periphery, epicardial fat lines within it-an occasional
sign of effusion-and pericardial cysts. Positive contrast
angiography may demonstrate wall thickening and some
dynamic features; arteriography may show coronary vessels
lying deep to an effusion or a cicatrix. Negative contrast
(carbon dioxide) right atriography, once useful, is no longer
needed. Computed tomography and allied techniques have
been increasingly valuable in identifying constriction, fat
pads, pericardial cysts. tumors and effusions. although for
effusions. echocardiography usually suffices. Technetium
pertechnetate , gallium-87 and other isotopes promise to
demonstrate pericardial fluid and epicardial inflammation,
but require further development.
Clinical Pericardial Disease
Pericardial friction. The rub, clinical hallmark of pericarditis, traditionally labeled a "to and fro" phenomenon,
was finally characterized as usually audible and recordable
as having three components (83). Prospective. multipleauscultator studies with phonocardiography in 100 patients
showed triphasic rubs in more than half of those with sinus
rhythm (84). Some biphasic ("to and fro") rubs were accounted for by absence of atrial systole, others by summation between diastolic and atrial (presystolic) rub components. Thus, most rubs are characteristically or potentially
triphasic. Fifteen patients had a monophasic rub, with one
confined to atrial systole. In a patient with complete atrioventricular block an atrial diastolic component produced a
quadriphasic rub (85), raising the question of the true mechanism of pericardial rubs; that is, atrial diastole must be a
feeble movement, and because rubs are common with effusion and tamponade (84), are they really friction (rubbing)
sounds?
Acute pericarditis and arrhythmias. It had been thought
that pericarditis must engulf the sinus node, lying a millimeter within the right atrial wall; this was traditionally thought
248
JAM cou. CARDlOl
1983:I:240--51
to cause arrhythmia in acute pericarditis. A prospective study
of 100 patients with acute pericarditis showed that arrhythmias were present only in a few of those with significant
heart disease (86). A retrospective study in a different patient
population confirmed this (73). Finally, elegant anatomic
studies (87) demonstrated that the sinus node is virtually
immune to involvement by surrounding acute pericarditis
and that arrhythmias occurred only in patients who had
disease of the myocardium or valves.
"New" forms of constriction. Traditionally termed
"chronic," constrictive pericarditis became uncommon in
Western countries by the 1950s, and acute and subacute
constrictive pericarditis were described (5). Uremic constriction recently appeared in patients permitted long survival by dialysis (88). Increased (though relatively small)
numbers of cases of postoperative constriction have followed the increase in cardiac surgery including coronary
bypass procedures (89). Intense mediastinal radiation therapy has added to the cases of constriction.
Surgery of the pericardium. Surgical indications in
pericardial disease have been unchanged except for earlier,
therefore easier, pericardiectomy in acute and subacute constriction (89). Resection of pericardial "windows" has become popular for biopsy, palliation of neoplastic effusions
and relief of resistant or relapsing acute pericarditis and
effusions, although resistant effusions are best treated by
extensive pericardiectomy. Formal studies are not available,
but clinical experience indicates that pericardial windows
tend to close, often with recurrence of effusion. Resection
or pericardiectomy for resistant inflammatory lesions is a
desperate measure with widely varying results; many cases
continue producing symptoms. A noteworthy advance in
managing tamponade is subxiphoid resection and exploration.
Right ventricular infarction. Contrary to previous
impressions, a functioning right ventricle is important to
maintain cardiac output, because right ventricular infarction
often produces a low output state. The pericardium has a
definite role: pericardiotomy after experimental right ventricular infarction improves left ventricular filling and output
(90). Moreover, right ventricular infarction shows restrictive
hemodynamics, owing to the presence of the pericardium,
with reduced left ventricular preload due to impaired right
ventricular systolic function and increased pericardial pressure.
Clinical investigation of cardiac tamponade. A landmark study (91) of 56 patients with cardiac tamponade quantitated the occurrence of clinical findings. Blood pressure
was often well maintained with systolic pressure 100 mm
Hg or more in 36 patients. Pulse pressure averaged 49 mm
Hg (40 mm Hg or more in 27). Pulsus paradoxus of 20 mm
Hg or more, present in 41 patients, involved the whole pulse
pressure in 12. Right ventricular dimensions increased and
left ventricular dimensions decreased during inspiration, except in one patient who had left ventricular dysfunction.
Fifty-two patients had an enlarged cardiac silhouette. Six-
SPODICK
teen patients with tamponade had a pericardial rub (consistent with previous observations that the rub is common
despite pericardial effusion, including tamponade)( 84). Heart
sounds were diminished in only 19 patients. Tachycardia
(heart rate 100 beats/min or more) was present in 43 patients.
Immunopathic pericarditis. A long-standing question
is how often pericarditis may be an immune or idiosyncratic
reaction, triggered, for example. by injuries and in response
to medications, and if such triggers provoke latent or smoldering infection, particularly by viruses. An important therapeutic challenge has been recurrent acute pericarditis in
the absence of overt pericardial infection. In many cases
recurrence is only suppressed with continuous or repetitive
anti-inflammatory treatment; some patients become
"hooked"-difficult or impossible to wean from corticosteroid agents (92).
A clinical mode! of immunopathic pericarditis is the postpericardiotomy syndrome. that is, acute postoperative but
"nonsurgical" pericarditis. often with effusion and pleural
involvement occurring in 15 to 20 ck of adult patients. The
elegant studies of Engle et al. (93) showed an incidence of
postpericardiotomy syndrome proportional to the extent of
surgical trauma in 36% of children over 2 years old. Antiheart antibody appeared in some patients whose diagnostic
high titers correlated with the clinical syndrome. In 70% of
patients with postpericardiotomy syndrome, a significant
rise in titer to one or more viruses was a nonspecific response
to agents prevalent in the community. The working hypothesis of Engle et al. was that postpericardiotomy syndrome is an immunologically determined response of the
epicardial myocardium, probably triggered by latent or fresh
viral illness; appearance of antiheart antibody is related to
the patient's age and previous immunologic experience.
The postmyocardial infarction syndrome, perhaps related
to the postpericardiotomy syndrome, occurs in very few
patients. lt is difficult to distinguish from infarct (epistenocardiac) pericarditis and the role of anti heart antibody has
been uncertain. iAutipericardial antibodies are unknown.)
Etiologic Forms of Pericardial Disease
Qualitative and quantitative changes in the vast etiologic
spectrum of pericarditis have followed changing prevalence,
effective treatment of infections, and conditions giving rise
to new forms of pericarditis (for example, dialysis has solved
most uremic pericarditis. but permits both "dialysis pericarditis" and uremic constriction).
Infective pericarditis. A recent review (94) summarized the status of infective pericarditis. In Western countries
purulent pericarditis is less frequent than in pre-antibiotic
days, occurring more often in children and in debilitated
and immunocompromised patients. The bacterial spectrum
includes an apparent decline in staphyococcal, streptococcal
and pneumococcal infections although epidemiologically
1 AM CaLL CARDIOL
1983;1:240-51
NORMAL AND DISEASED PERICARDIUM
sound studies are lacking. Pus still should be evacuated
promptly and quantitatively, usually by surgery, because
pyogenic infections tend to cause tamponade and constriction. Fortunately, the level reached by antibiotics in pericardial fluid is excellent and the serum level can be used to
judge the pericardial level (95). Tuberculous pericarditis
has decreased in incidence, and is no longer the prime cause
of constriction. although it is a popular "rule out." Viral
pericarditis probably accounts for most community-acquired infections (96). although viral cultures usually fail:
fourfold or greater increases in convalescent serum titer are
usual but, because of the benignity of most infections. are
not tested. The most common viruses are the Coxsackie
group. echoviruses and. probably. adenovirus. Individual
cases of rickettsial. mycotic. parasitic and many hitherto
"uncommon" organisms like Legionella pneumophilia continue to be reported. In post-surgical, debilitated and immunocompromised hosts. gram-negative bacilli are relatively common. Among children. Haemophilus infiuenzae
pericarditis still has an ominous prognosis for exceptionally
rapid tamponade and constriction. The influence of antibiotics on purulent pericarditis was summarized (94): I)
incidence has decreased; 2) survival has increased; 3) drainage is still necessary; 4) some cases are masked; 5) resistant
and unusual organisms have appeared; 6) there are more
hospital-acquired cases; and 7) there is a greater post-surgical incidence (especially cardiac surgery).
Wounds. Chest, heart and pericardial wounds produce
major emergencies, particularly tamponade that is not always readily recognized. Many signs may be lacking because of rapid pericardial hemorrhage with blood volume
depletion. Experience favors early surgical exploration and
drainage (97).
Uremic pericarditis. This condition usually appears
shortly before or after beginning dialysis, which has made
it newly important (88,98). because previous treatment was
ineffective and pericarditis was a harbinger of death (6).
The etiology is unknown because intrapericardial creatinine
and related substances do not cause pericarditis. Yet the
vast majority have a blood urea nitrogen (BUN) level of 60
mg/lOO ml or more. Volume depletion. for example. during
dialysis, may precipitate latent tamponade. Uremic constriction has become a result of long survival (99). With
time and satisfactory dialysis. some patients now develop
dialysis pericarditis. which can occur at normal BUN levels.
Some patients have intercurrent infection. traditionally
pneumoccal, but now presumably mostly viral. (Hepatitis
virus. common in dialysis units. is associated with pericarditis.) Infected uremic patients may be those with typical
stage I electrocardiographic changes, such ST-T changes
being rare in uremia because even severe uremic pericarditis
usually spares the myocardium. In uncomplicated cases.
treatment is intense dialysis. Management of tamponade in
uremic or dialysis pericarditis is by pericardiocentesis with
249
prolonged catheter or surgical drainage, or pericardiectomy
(88,98). Medical treatment with intrapericardial or systemic
anti-inflammatory agents is controversial because of the lack
of a randomized controlled trial.
Radiation pericarditis. Although pericarditic effects of
therapeutic radiation had been described (5.6), widespread
use of mediastinal radiation for malignancy (particularly
lymphomas and Hodgkin's disease) greatly multiplied the
cases. A mediastinal dose of 4.000 rads or greater will
produce acute fibrinous pericarditis and damage capillary
and lymphatic endothelium. obstructing these vessels to
produce effusion and tamponade; some patients develop
local or generalized constriction (100).
Idiopathic pericarditis. The well known syndrome of
idiopathic (formerly" acute benign") pericarditis occurring
mostly in men, appears usually to be of viral origin. Some
specific diseases. for example. lupus erythematosus. may
first appear as an idiopathic pericarditis. so that women with
"Idiopatbic " pericarditis should be appropriately tested.
Iatrogenic pericarditis. A host of physicians' treatments and maneuvers in addition to radiation and dialysis
pericarditis. can affect the pericardium; this is seen most
frequently in response to a variety of medications, notably
procainamide and hydralazine (and sometimes in connection
with drug-induced lupus) which leads to acute pericarditis
and. rarely. to constriction. The great increase in cardiac
surgery has produced much more of both the usual surgical
pericarditis and delayed post-surgical (immunopathic'?) pericarditis as well as immediate and delayed postoperative
cardiac tamponade and constriction. During surgery. the
delicate mesothelium probably is always lost or widely disrupted and. in appropriate patients. an immediate. delayed
or recurrent pericardial syndrome develops.
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